PolyFun S-LDSC

Intro

I ran S-LDSC (comes with PolyFun) jointly on all cancer-related and immune annotations. I used a subset of the baseline LD annotations with MAF bins, LD, and other SNP statistics. I did this for four cancer GWAS: breast, prostate, colorectal, ovarian.

Annotations were obtained from ENCODE and ROADMAP.

Comparison of Immune Enrichment

Below is the LDSC enrichment (prop h2 / prop of SNPs) for ROADMAP immune ChIP-seq peaks. These were jointly run with cancer-specific annotations (shown below).

brca <- read.delim('../results/BRCA_enrichment.results', header=T, sep="", stringsAsFactors = F)
brca <- brca[,c("Category","Enrichment")]
prad <- read.delim('../results/PRAD_enrichment.results', header=T, sep="", stringsAsFactors = F)
prad <- prad[, c("Category","Enrichment")]
coad <- read.delim('../results/COAD_enrichment.results', header=T, sep="", stringsAsFactors = F)
coad <- coad[, c("Category","Enrichment")]
ov <- read.delim('../results/OV_enrichment.results', header=T, sep="", stringsAsFactors = F)
ov <- ov[, c("Category","Enrichment")]
enrich.df <- plyr::join_all(list(brca, prad, coad, ov), by = 'Category', type = 'inner')
enrich.df <- enrich.df[c(1:101), ]
colnames(enrich.df) <- c("Category","BRCA","PRAD","COAD","OV")
enrich.df <- enrich.df[!(enrich.df$Category %in% "Cancer_Drivers"), ] # this is common to all so we remove it
immune.annots <- enrich.df$Category
row.names(enrich.df) <- enrich.df$Category
enrich.df$Category <- NULL

labs <- sapply(strsplit(row.names(enrich.df), split = '-'), function(x){x[length(x)]})
labs <- sapply(strsplit(labs, split='_'), function(x){x[length(x)]})
enrich.df <- enrich.df[order(labs),]
lab.df <- data.frame(Type=sort(labs), row.names = row.names(enrich.df))
pheatmap::pheatmap(enrich.df, cluster_rows = F, cluster_cols = F, border_color = NA, annotation_row = lab.df, show_rownames = F)

Breast cancer

sldsc <- read.delim('../results/BRCA_enrichment.results', header=T, sep="",stringsAsFactors = F)
sldsc <- sldsc[c(1:121),]
sldsc$ci <- 1.96*sldsc$Enrichment_std_error
non.immune <- sldsc[!(sldsc$Category %in% immune.annots), ]
immune <- sldsc[(sldsc$Category %in% immune.annots), ]
ggplot(non.immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

labs <- sapply(strsplit(immune$Category, split = '-'), function(x){x[length(x)]})
labs <- sapply(strsplit(labs, split='_'), function(x){x[length(x)]})
immune$Category <- factor(immune$Category, levels = immune$Category[order(labs)])

ggplot(immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

Prostate cancer

sldsc <- read.delim('../results/PRAD_enrichment.results', header=T, sep="", stringsAsFactors = F)
sldsc <- sldsc[c(1:129),]
sldsc$ci <- 1.96*sldsc$Enrichment_std_error
non.immune <- sldsc[!(sldsc$Category %in% immune.annots), ]
immune <- sldsc[(sldsc$Category %in% immune.annots), ]
non.immune$Category <- gsub(pattern = '_0', replacement = '', x = non.immune$Category)
ggplot(non.immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

labs <- sapply(strsplit(immune$Category, split = '-'), function(x){x[length(x)]})
labs <- sapply(strsplit(labs, split='_'), function(x){x[length(x)]})
immune$Category <- factor(immune$Category, levels = immune$Category[order(labs)])
ggplot(immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

Colorectal cancer

sldsc <- read.delim('../results/COAD_enrichment.results', header=T, sep="", stringsAsFactors = F)
sldsc <- sldsc[c(1:117),]
sldsc$ci <- 1.96*sldsc$Enrichment_std_error
non.immune <- sldsc[!(sldsc$Category %in% immune.annots), ]
immune <- sldsc[(sldsc$Category %in% immune.annots), ]
ggplot(non.immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

labs <- sapply(strsplit(immune$Category, split = '-'), function(x){x[length(x)]})
labs <- sapply(strsplit(labs, split='_'), function(x){x[length(x)]})
immune$Category <- factor(immune$Category, levels = immune$Category[order(labs)])
ggplot(immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

Ovarian cancer

None of these annotations were ovarian cancer specific. These are all from healthy ovary tissue. TCGA did not have OV cancer ATAC-seq peaks calls.

sldsc <- read.delim('../results/OV_enrichment.results', header=T, sep="", stringsAsFactors = F)
sldsc <- sldsc[c(1:108),]
sldsc$ci <- 1.96*sldsc$Enrichment_std_error
non.immune <- sldsc[!(sldsc$Category %in% immune.annots), ]
immune <- sldsc[(sldsc$Category %in% immune.annots), ]
ggplot(non.immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')

labs <- sapply(strsplit(immune$Category, split = '-'), function(x){x[length(x)]})
labs <- sapply(strsplit(labs, split='_'), function(x){x[length(x)]})
immune$Category <- factor(immune$Category, levels = immune$Category[order(labs)])
ggplot(immune, aes(x=Category, y=Enrichment)) + 
  geom_point() + 
  coord_flip() +
  geom_hline(yintercept = 1, color="red", linetype="dashed") +
  geom_errorbar(aes(ymin=Enrichment-ci, ymax=Enrichment+ci), width=.2) +
  theme(text = element_text(size=14),
        panel.grid.major = element_blank(), 
        panel.grid.minor = element_blank(),
        axis.text.y = element_text(size=10)) +
  ylab('Enrichment') + 
  xlab('Category')